Work will continue on the isolation and identification of new metabolites of vitamin D and vitamin A found in plasma, tissues and bile of rats and chicks given appropriately labeled compounds. The mechanism whereby metabolites of vitamin D and A are biosynthesized will be studied as will the regulation of these processes using cell culture and enzymological techniques. The mechanism whereby 1,25-(OH)2D3 functions in the target tissues will continue to occupy major interest, especially the isolation to homogeneity of the 1,25-(OH)2D3 receptor protein. Work will be initiated on the differentiation of teratocarcinoma, F9 cells in response to retinoic acid. The gene products produced by the response of these cells to retinoic acid will be studied using two-dimensional gel electrophoresis. The attempted purification of the vitamin K-dependent carboxylase and the study of the vitamin K epoxy reductase will continue. Intermediates in protein processing involved in prothrombin biosynthesis in response to vitamin K will be identified. The pathway of selenium incorporation into glutathione peroxidase will be elucidated. The pro-oxidant effect of Adriamycin and its counteraction or potentiation by vitamin E and selenium will be determined. Work will continue on the relationship between selenium vitamin E and vitamin D intoxication. The possible involvement of dietary manganese in the development of brain damage induced by vitamin E deficiency in chicks work will investigated.